RESUMEN

Currently, mitochondrial dysfunction caused by oxidative stress is a growing concern in degenerative diseases, notably intervertebral disc degeneration (IVDD). Dysregulation of the balance of mitochondrial quality control (MQC) has been considered the key contributor, while it's still challenging to effectively harmonize different MQC components in a simple and biologically safe way. Hydrogen gas (H2) is a promising mitochondrial therapeutic molecule due to its bio-reductivity and diffusibility across cellular membranes, yet its relationship with MQC regulation remains unknown. Herein, we propose a mitochondrial 'Birth-Death' coordinator achieved by an intelligent hydrogen nanogenerator (Fe@HP-OD), which can sustainably release H2 in response to the unique microenvironment in degenerated IVDs. Both in vitro and in vivo results prove alleviation of cellular oxidative stress and restoration of nucleus pulposus cells function, thereby facilitating successful IVD regeneration. Significantly, this study for the first time proposes the mitochondrial 'Birth-Death' coordination mechanism: 1) attenuation of overactivated mitochondrial 'Death' process (UPRmt and unselective mitophagy); and 2) activation of Adenosine 5'-monophosphate-activated protein kinase (AMPK) signaling pathway for mitochondrial 'Birth-Death' balance (mitochondrial biogenesis and controlled mitophagy). These pioneering findings can fill in the gaps in molecular mechanisms for H2 regulation on MQC homeostasis, and pave the way for future strategies towards restoring equilibrium of MQC system against degenerative diseases.

Asunto(s)

Hidrógeno , Degeneración del Disco Intervertebral , Mitocondrias , Estrés Oxidativo , Hidrógeno/química , Animales , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Regeneración/efectos de los fármacos , Disco Intervertebral/efectos de los fármacos , Humanos , Mitofagia/efectos de los fármacos , Ratas Sprague-Dawley , Masculino , Núcleo Pulposo/metabolismo , Ratas

RESUMEN

Implant-associated infection (IAI) has become an intractable challenge in clinic. The healing of IAI is a complex physiological process involving a series of spatiotemporal connected events. However, existing titanium-based implants in clinic suffer from poor antibacterial effect and single function. Herein, a versatile surface platform based on the presentation of sequential function is developed. Fabrication of titania nanotubes and poly-γ-glutamic acid (γ-PGA) achieves the efficient incorporation of silver ions (Ag+) and the pH-sensitive release in response to acidic bone infection microenvironment. The optimized PGA/Ag platform exhibits satisfactory biocompatibility and converts macrophages from pro-inflammatory M1 to pro-healing M2 phenotype during the subsequent healing stage, which creates a beneficial osteoimmune microenvironment and promotes angio/osteogenesis. Furthermore, the PGA/Ag platform mediates osteoblast/osteoclast coupling through inhibiting CCL3/CCR1 signaling. These biological effects synergistically improve osseointegration under bacterial infection in vivo, matching the healing process of IAI. Overall, the novel integrated PGA/Ag surface platform proposed in this study fulfills function cascades under pathological state and shows great potential in IAI therapy.

Asunto(s)

Antibacterianos , Ácido Poliglutámico , Plata , Titanio , Animales , Titanio/química , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Ratones , Ácido Poliglutámico/química , Ácido Poliglutámico/análogos & derivados , Plata/química , Plata/farmacología , Propiedades de Superficie , Nanotubos/química , Células RAW 264.7 , Infecciones Relacionadas con Prótesis/tratamiento farmacológico , Oseointegración/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Osteoblastos/efectos de los fármacos , Osteoblastos/citología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Masculino , Cicatrización de Heridas/efectos de los fármacos , Prótesis e Implantes

RESUMEN

Complex tissue damage accompanying with bacterial infection challenges healthcare systems globally. Conventional tissue engineering scaffolds normally generate secondary implantation trauma, mismatched regeneration and infection risks. Herein, we developed an easily implanted scaffold with multistep shape memory and photothermal-chemodynamic properties to exactly match repair requirements of each part from the tissue defect by adjusting its morphology as needed meanwhile inhibiting bacterial infection on demand. Specifically, a thermal-induced shape memory scaffold was prepared using hydroxyethyl methacrylate and polyethylene glycol diacrylate, which was further combined with the photothermal agent iron tannate (FeTA) to produce NIR light-induced shape memory property. By varying ingredients ratios in each segment, this scaffold could perform a stepwise recovery under different NIR periods. This process facilitated implantation after shape fixing to avoid trauma caused by conventional methods and gradually filled irregular defects under NIR to perform suitable tissue regeneration. Moreover, FeTA also catalyzed Fenton reaction at bacterial infections with abundant H2O2, which produced excess ROS for chemodynamic antibacterial therapy. As expected, bacteriostatic rate was further enhanced by additional photothermal therapy under NIR. The in vitro and vivo results showed that our scaffold was able to perform high efficacy in both antibiosis, inflammation reduction and wound healing acceleration, indicating a promising candidate for the regeneration of complex tissue damage with bacterial infection.

Asunto(s)

Antibacterianos , Andamios del Tejido , Cicatrización de Heridas , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/uso terapéutico , Animales , Andamios del Tejido/química , Ratones , Cicatrización de Heridas/efectos de los fármacos , Rayos Infrarrojos , Terapia Fototérmica , Ingeniería de Tejidos/métodos , Taninos/química , Taninos/farmacología , Materiales Inteligentes/química , Staphylococcus aureus/efectos de los fármacos , Masculino , Polietilenglicoles/química

RESUMEN

Radiotherapy as a mainstay of in-depth cervical cancer (CC) treatment suffers from its radioresistance. Radiodynamic therapy (RDT) effectively reverses radio-resistance by generating reactive oxygen species (ROS) with deep tissue penetration. However, the photosensitizers stimulated by X-ray have high toxicity and energy attenuation. Therefore, X-ray responsive diselenide-bridged mesoporous silica nanoparticles (DMSNs) are designed, loading X-ray-activated photosensitizer acridine orange (AO) for spot blasting RDT like Trojan-horse against radio-resistance cervical cancer (R-CC). DMSNs can encapsulate a large amount of AO, in the tumor microenvironment (TME), which has a high concentration of hydrogen peroxide, X-ray radiation triggers the cleavage of diselenide bonds, leading to the degradation of DMSNs and the consequent release of AO directly at the tumor site. On the one hand, it solves the problems of rapid drug clearance, adverse distribution, and side effects caused by simple AO treatment. On the other hand, it fully utilizes the advantages of highly penetrating X-ray responsive RDT to enhance radiotherapy sensitivity. This approach results in ROS-induced mitochondria damage, inhibition of DNA damage repair, cell cycle arrest and promotion of cancer cell apoptosis in R-CC. The X-ray responsive DMSNs@AO hold considerable potential in overcoming obstacles for advanced RDT in the treatment of R-CC.

Asunto(s)

Nanopartículas , Dióxido de Silicio , Humanos , Animales , Rayos X , Nanopartículas/química , Femenino , Dióxido de Silicio/química , Ratones , Neoplasias del Cuello Uterino/terapia , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/patología , Especies Reactivas de Oxígeno/metabolismo , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Tolerancia a Radiación/efectos de los fármacos , Microambiente Tumoral/efectos de los fármacos , Ratones Desnudos , Células HeLa , Ratones Endogámicos BALB C , Apoptosis/efectos de los fármacos , Línea Celular Tumoral

RESUMEN

Bacterial infections and long-term inflammation cause serious secondary damage to chronic diabetic wounds and hinder the wound healing processes. Currently, multifunctional hydrogels have shown promising effects in chronic wound repair. However, traditional hydrogels only keep the wound moist and protect it from bacterial infection, and cannot provide mechanical force to contract the wound edges to achieve facilitated wound closure. Here, an asymmetric composite dressing was created by combining biaxially oriented nanofibers and hydrogel, inspired by the double-layer structure of the traditional Chinese medicinal plaster patch, for managing chronic wounds. Specifically, electrospun Poly-(lactic acid-co-trimethylene carbonate) (PLATMC) nanofibers and methacrylate gelatin (GelMa) hydrogel loaded with Epinecidin-1@chitosan (Epi-1@CS) nanoparticles are assembled as the temperature-responsive self-contracting nanofiber/hydrogel (TSNH) composite dressing. The substrate layer of PLATMC nanofibers combines topological morphology with material properties to drive wound closure through temperature-triggered contraction force. The functional layer of GelMa hydrogel is loaded with Epi-1@CS nanoparticles that combine satisfactory cytocompatibility, and antioxidant, anti-inflammatory, and antibacterial properties. Strikingly, in vivo, the TSNH dressing could regulate the diabetic wound microenvironment, thereby promoting collagen deposition, facilitating angiogenesis, and reducing the inflammatory response, which promotes the rapid healing of chronic wounds. This study highlights the potential of synergizing mechanical and biochemical signals in enhancing chronic wound treatment. Overall, this TSNH composite dressing is provided as a reliable approach to solving the long-standing problem of chronically infected wound healing.

RESUMEN

Objectives: The aim of this study was to investigate the mechanism of itaconate's potential effect in diabetic kidney disease.Methods: Renal immune responsive gene 1 (IRG1) levels were measured in db/db mice and streptozotocin (STZ) + high-fat diet (HFD)-induced diabetic mice. Irg1 knockout mice were generated. db/db mice were treated with 4-octyl itaconate (4-OI, 50 mg/kg), a derivative of itaconate, for 4 weeks. Renal function and morphological changes were investigated. Ultrastructural alterations were determined by transmission electron microscopy.Results: Renal IRG1 levels were reduced in two diabetic models. STZ+HFD-treated Irg1 knockout mice exhibited aggravated renal tubular injury and worsened renal function. Treatment with 4-OI lowered urinary albumin-to-creatinine ratio and blood urea nitrogen levels, and restored renal histological changes in db/db mice. It improved mitochondrial damage, increased expressions of peroxisome-proliferator-activated receptor γ coactivator-1α (PGC-1α) and mitochondrial transcription factor A (TFAM) in the renal cortex of db/db mice. These were confirmed in vitro; 4-OI improved high glucose-induced abnormal mitochondrial morphology and TFAM expression in HK-2 cells, effects that were inhibited by PGC-1α silencing. Moreover, 4-OI reduced the number of apoptotic cells in the renal cortex of db/db mice. Further study showed that 4-OI increased renal Nrf2 expression and decreased oxidative stress levels in db/db mice. In HK-2 cells, 4-OI decreased high glucose-induced mitochondrial ROS production, which was reversed by Nrf2 silencing. Nrf2 depletion also inhibited 4-OI-mediated regulation of PGC-1α, TFAM, and mitochondrial apoptotic protein expressions.Conclusions: 4-OI attenuates renal tubular injury in db/db mice by activating Nrf2 and promoting PGC-1α-mediated mitochondrial biogenesis.

Asunto(s)

Diabetes Mellitus Experimental , Nefropatías Diabéticas , Ratones Noqueados , Factor 2 Relacionado con NF-E2 , Biogénesis de Organelos , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma , Succinatos , Animales , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Ratones , Succinatos/farmacología , Succinatos/uso terapéutico , Nefropatías Diabéticas/metabolismo , Nefropatías Diabéticas/tratamiento farmacológico , Nefropatías Diabéticas/patología , Nefropatías Diabéticas/prevención & control , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/metabolismo , Masculino , Humanos , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Estrés Oxidativo/efectos de los fármacos , Factores de Transcripción/metabolismo , Túbulos Renales/patología , Túbulos Renales/efectos de los fármacos , Túbulos Renales/metabolismo , Ratones Endogámicos C57BL , Apoptosis/efectos de los fármacos

RESUMEN

Myelin oligodendrocyte glycoprotein antibody-associated disease is a group of central nervous system demyelinating disorders caused by autoantibodies. While myelin oligodendrocyte glycoprotein antibody-associated disease typically presents as optic neuritis and myelitis in adults, this case report details a patient with brainstem lesions. A 45-year-old male presented with episodes of vertigo, nystagmus, and diplopia in left lateral gaze, which had persisted for 2 months, accompanied by headache. Computed tomography showed hyperdensity extending from the left side of the pons to the middle cerebellar peduncle. Magnetic resonance imaging revealed lesions exhibiting heterogeneous diffusion restriction, with enhancement that included granular and linear patterns. 18F-fluorodeoxyglucose positron emission tomography demonstrated increased uptake in these lesions. Following further evaluation, myelin oligodendrocyte glycoprotein antibody-associated disease was diagnosed. Treatment with high-dose corticosteroids initially alleviated symptoms, but symptoms flared upon reduction of the steroids. This case underscores the importance of considering myelin oligodendrocyte glycoprotein antibody-associated disease in the differential diagnosis of brainstem lesions and discusses distinguishing imaging features from similar conditions.

RESUMEN

The integration of magnetic nanoparticles (MNPs) into biomaterials offers exciting opportunities for tissue engineering as they enable better control over cell guidance, release of bioactive factors and tissue maturation. Despite their potential, challenges such as the heterogeneity of MNPs, their cytotoxicity and the need for precise control of MNP`s properties hinder their widespread application. Overcoming these challenges will require new interdisciplinary efforts and technological advances, including the development of mathematical tools and additional elaborations to ensure the biocompatibility of MNPs.

RESUMEN

As a kind of unique biomimetic macromolecule, polydopamine (PDA) have prominent in-situ reduction ability and interfacial adhesion. In this work, combined with in-situ reduction ability of PDA and excellent magnetic response performance of nickel foam (NF), a strategy was designed to fabricate a series of NF@PDA@AgNPs as magnetic-responsive surface enhancement Raman scattering (SERS) substrates for highly sensitive Rhodamine B (RhB) detection in chili powder. With crystal violet (CV) as probe molecule, the detection limit of SERS substrate could achieve 10-10 M, and the enhancement factor was as high as to 2.22 × 107. In addition, the NF@PDA@AgNPs SERS substrates showed excellent magnetic separation efficiency, good SERS uniformity and storage stability. More importantly, these substrates could achieve highly efficient collection and sensitive detection of RhB residues in chili powder by magnetic adsorption method, and the detection of limit was as low as to be 10-6 g/g. These NF@PDA@AgNPs substrates would be a great prospect for rapid and efficient pernicious contaminant detection in the chemical and biological fields.

RESUMEN

Entomopathogenic fungi offer an ecologically sustainable and highly effective alternative to chemical pesticides for managing plant pests. However, the efficacy of mycoinsecticides in pest control suffers from environmental abiotic stresses, such as solar UV radiation and temperature fluctuations, which seriously hinder their practical application in the field. Herein, we discovered that the synthetic amphiphilic thermal-responsive polymers are able to significantly enhance the resistance of Metarhizium robertsii conidia against thermal and UV irradiation stresses. The thermosensitive polymers with extremely low cytotoxicity and good biocompatibility can be engineered onto the M. robertsii conidia surface by anchoring hydrophobic alkyl chains. Further investigations revealed that polymer supplementation remarkably augmented the capacity for penetration and the virulence of M. robertsii under heat and UV stresses. Notably, broad-spectrum entomopathogenic fungi can be protected by the polymers. The molecular mechanism was elucidated through exploring RNA sequencing and in vivo/vitro enzyme activity assays. This work provides a novel avenue for fortifying the resilience of entomopathogenic fungi, potentially advancing their practical application as biopesticides.

Asunto(s)

Metarhizium , Polímeros , Metarhizium/genética , Metarhizium/química , Metarhizium/efectos de la radiación , Polímeros/química , Polímeros/farmacología , Calor , Estrés Fisiológico , Rayos Ultravioleta , Esporas Fúngicas/efectos de los fármacos , Esporas Fúngicas/efectos de la radiación , Animales , Control Biológico de Vectores

RESUMEN

Based on the modified cross-linking of the degradable natural polymers chitosan oligosaccharides (COS) and gelatin (GEL) via introduction of a functional bridge 3,3'-dithiodipropionic acid, this study constructed an environmentally responsive dinotefuran (DNF) delivery system (DNF@COS-SS-GEL). The introduction of the disulfide bond (-S-S-) endowed DNF@COS-SS-GEL with redox-responsive properties, allowing for the rapid release of pesticides when stimulated by glutathione (GSH) in the simulated insect. Compared with commercial DNF suspension concentrate (DNF-SC), DNF@COS-SS-GEL showed superior wet spreading and retention performance on cabbage leaves with a reduced contact angle (57°) at 180 s and 4-fold increased retention capacity after rainfall washout. Nanoencapsulation effectively improved the UV-photostability with only a 31.4% decomposition rate of DNF@COS-SS-GEL at 96 h. The small scale and large specific surface area resulted in excellent uptake and transportation properties in plants as well as higher bioactivity against Plutella xylostella larvae. This study will help promote sustainable agricultural development by reducing environmental pollution through improved pesticide utilization.

Asunto(s)

Brassica , Quitosano , Oxidación-Reducción , Plaguicidas , Hojas de la Planta , Animales , Hojas de la Planta/química , Hojas de la Planta/metabolismo , Brassica/química , Brassica/metabolismo , Quitosano/química , Plaguicidas/química , Plaguicidas/farmacología , Plaguicidas/metabolismo , Mariposas Nocturnas/efectos de los fármacos , Mariposas Nocturnas/metabolismo , Mariposas Nocturnas/química , Larva/crecimiento & desarrollo , Larva/efectos de los fármacos , Polímeros/química , Sistemas de Liberación de Medicamentos/instrumentación , Neonicotinoides/química , Neonicotinoides/metabolismo , Neonicotinoides/farmacología , Insecticidas/química , Insecticidas/farmacología , Gelatina/química

RESUMEN

The antimicrobial and pro-healing properties remain critical clinical objectives for skin wound management. However, the escalating problem of antibiotic overuse and the corresponding rise in bacterial resistance necessitates an urgent shift towards an antibiotic-free approach to antibacterial treatment. The quest for antimicrobial efficacy while accelerating wound healing without antibiotic treatment have emerged as innovative strategies in skin wound treatment. Here, a dual-function hydrogel with antimicrobial and enhanced tissue-healing properties was developed by utilizing cyclodextrin, ferrocene, polyethyleneimine (PEI), and Bletilla striata polysaccharide (BSP), through multiple non-covalent interactions, which can intelligently release BSP by recognizing the wound inflammatory microenvironment through the cyclodextrin-ferrocene unit. Moreover, the porosity (65 % - 85 %), Young's modulus (400 KPa - 140 KPa), and DPPH scavenge rate (18 % - 40 %) of the hydrogel are modulated by varying the BSP content. The hydrogel exhibits outstanding antibacterial properties (98.3 % reduction of Escherichia coli observed after exposure to HTFC@BSP-20 for 24 h) and favorable biocompatibility. Furthermore, in a rat full-thickness skin wound model, the dual-function hydrogel significantly accelerates wound healing, increased CD31 expression promotes vascular regeneration, reduced TNF-α express and inhibited the inflammation. This multifunctional ROS responsive hydrogel provides a new perspective for antibiotics-free treatment of skin injuries.

Asunto(s)

Antibacterianos , Vendajes , Hidrogeles , Polisacáridos , Especies Reactivas de Oxígeno , Cicatrización de Heridas , Cicatrización de Heridas/efectos de los fármacos , Hidrogeles/química , Hidrogeles/farmacología , Animales , Polisacáridos/química , Polisacáridos/farmacología , Ratas , Especies Reactivas de Oxígeno/metabolismo , Antibacterianos/farmacología , Antibacterianos/química , Inflamación/tratamiento farmacológico , Orchidaceae/química , Escherichia coli/efectos de los fármacos , Humanos , Piel/efectos de los fármacos , Ciclodextrinas/química , Ciclodextrinas/farmacología , Ratas Sprague-Dawley , Masculino , Compuestos Ferrosos/química , Compuestos Ferrosos/farmacología , Metalocenos

RESUMEN

Helicobacter pylori is the primary cause of gastric adenocarcinoma, which afflicts more than half of the world's population and seriously affects human health. However, achieving efficient treatment of H. pylori infection by effective drug delivery and bioavailability after oral administration remains a challenge due to the harsh microenvironment, short drug retention time, and physiological barriers in the stomach. Moreover, H. pylori has shown resistance to many clinical antibiotics. Antimicrobial peptides (AMPs) exhibit substantial therapeutic efficacy against H. pylori, while they are not likely to induce drug resistance, suggesting their potential utility for the treatment of diseases related to H. pylori. In this paper, we report the design and synthesis of an AMP (GE33) hydrogel with pH-responsive and controlled peptide release properties, in which the minimal inhibitory concentration of the AMP against H. pylori is as low as 1 µg/mL. GE33 self-assembles into a stable peptide hydrogel under neutral pH conditions but decomposes into monomers or oligomers under acidic conditions. Upon oral administration of the hydrogel, the acidic gastric environment would facilitate rapid release of active AMP molecules from the hydrogel and immediate targeting of H. pylori in the stomach wall. Additionally, the remaining peptide is protected in the hydrogel, extending its retention time in the stomach, so that persistent drug release is achieved. The controlled and sustained release manner of the active molecule GE33, which enhances drug bioavailability, along with its excellent bactericidal efficacy opens a great potential for treating H. pylori infection.

RESUMEN

Nanocatalysts with photodynamic therapy (PDT) and chemodynamic therapy (CDT) are excellent for tumor therapy. However, it is still challenging to achieve complete tumor eradication due to the drawbacks of limited penetration depth of intratumoural tissues, hypoxia and complexity of the tumor microenvironment (TME). Herein, we fabricated an integrated multifunctional nanoreactor (LuAG:Tb/Ce-RB@ZIF-8-Au2Pt-HA, LRZAPH) combining scintillating nanoparticles (SCNPs, LuAG:Tb/Ce), a metal-organic framework (ZIF-8), and bimetallic Au2Pt for X-ray-triggered PDT and dual noble-metal nanozyme catalyzed CDT. Such a nanoreactor not only significantly enhanced the PDT effect under X-ray irradiation through full resonance energy transfer from LuAG:Tb/Ce scintillator to Ross Bengal (RB), but also facilitated the reactive oxygen species (ROS) and oxygen (O2) production through the excellent peroxidase-like (POD-like) and catalase-like (CAT-like) catalytic properties of Au2Pt nanozymes. O2 also alleviates hypoxia in intratumoural tissues during coordinated PDT. In addition, the dissociation behavior of ZIF-8 with pH-responsive and targeted of hyaluronic acid (HA) in acidic TME significantly enhanced the therapeutic efficacy of LRZAPH nanocatalysts. Significantly, the high tumor growth inhibition rate of 93 % was revealed due to radiotherapy (RT)/PDT/CDT synergetic therapy in vivo, which minimized the toxic and side effects of conventional clinical radiotherapy/chemotherapy on human. The synergistic effect of LRZAPH nanocatalysts on PDT and catalytically induced CDT is expected to provide new pathways for effective treatment of deep tumors.

RESUMEN

Neutrophil elastase (NE) is a protease released by activated neutrophils in the brain parenchyma after cerebral ischemia, which plays a pivotal role in the regulation of neutrophil extracellular traps (NETs) formation. The excess NETs could lead to blood-brain barrier (BBB) breakdown, overwhelming neuroinflammation, and neuronal injury. While the potential of targeting neutrophils and inhibiting NE activity to mitigate ischemic stroke (IS) pathology has been recognized, effective strategies that inhibit NETs formation remain under-explored. Herein, a biomimic multifunctional nanoplatform (HM@ST/TeTeLipos) was developed for active NE targeting and IS treatment. The core of the HM@ST/TeTeLipos consisted of sivelestat-loaded ditelluride-containing liposomes with ROS-responsive and NE-inhibiting properties. The outer shell was composed of platelet-neutrophil hybrid membrane vesicles (HMVs), which acted to hijack neutrophils and neutralize proinflammatory cytokines. Our studies revealed that HM@ST/TeTeLipos could effectively inhibit NE activity, thereby suppressing the release of NETs, impeding the activation of the AIM2 inflammasome, and consequently redirecting the immune response away from a pro-inflammatory M1 microglia phenotype. This resulted in enhanced neurovascular remodeling, reduced BBB disruption, and diminished neuroinflammation, ultimately promoting neuron survival. We believe that this innovative approach holds significant potential for improving the treatment of IS and various NE-mediated inflammatory diseases.

RESUMEN

Ghosal hematodiaphyseal dysplasia (GHDD) is an autosomal recessive disorder characterized by diaphyseal dysplasia of long bones, bone marrow fibrosis, and steroid-responsive anemia. Patients with this disease have a mutation in the thromboxane-AS1 (TBXAS1) gene located on chromosome 7q33.34. They present with short stature, varying grades of myelofibrosis, and, hence cytopenias. Patients with the above presentation were evaluated through clinical presentation, X-ray of long bones, bone marrow examinations, and confirmed by genetic testing. In this article, we present two cases: The first case is a 3-year-old boy who presented with progressive pallor and ecchymotic patches for a year. On investigation, he had bicytopenia and bone marrow fibrosis. His anemia was steroid responsive and was finally diagnosed as GHDD. The second case is a 20-month-old girl who presented with blood in stools, developmental delay, anemia, and increased intensity of long bones on X-ray. Since other investigations were normal, suspicion of GHDD was raised, and a genetic workup was conducted which suggested mutation in TBXAS1 gene, confirming the diagnosis of GHDD. Children with refractory anemia and cortical thickening on skeletogram should always be evaluated for dysplasias. Timely treatment with steroids reduces transfusion requirements and halts bone damage, thus leading to better growth and improved quality of life.

Asunto(s)

Anemia , Humanos , Masculino , Preescolar , Femenino , Anemia/etiología , Anemia/tratamiento farmacológico , Mutación , Lactante , Osteocondrodisplasias/genética , Osteocondrodisplasias/complicaciones , Osteocondrodisplasias/diagnóstico , Resultado del Tratamiento , Radiografía , Esteroides/uso terapéutico , Anemia Refractaria

RESUMEN

Multiscale particle size functional pesticide carriers can provide more efficient protection for plants, but this protection is difficult to achieve via single-scale formulation technology. This study presents a novel one-step method for the preparation of lignin-based micro/nanocapsules with controllable proportions within a unified system. This strategy enables the adjustment of the proportion of nanocapsules to between 18.81% and 85.21%. The microcapsules (MCs) vary in diameter from 2 to 3 µm, whereas the nanocapsules (NCs) span from 160 to 220 nm, with an encapsulation efficiency exceeding 90%. An increased proportion of NCs in the system leads to faster release, heightened sensitivity to UV light, and enhanced penetration into the leaves. During Phytophthora capsici (P. capsici) infection, the NCs in the leaves interact with the defensive enzymes of the plant to quickly respond. Moreover, an optimal balance of MCs and NCs is key to effective fungicide use, not just a higher concentration of NCs. A 65:35 ratio of NCs to MCs ensures effective inhibition of P. capsici outside leaves and a rapid response to leaf invasion. This study enhances fungicide efficiency and advances the development of nanoresponsive fungicides to promote sustainable agricultural practices.

RESUMEN

Low-density magnesium (Mg) alloys are excellent engineering materials, and can significantly reduce energy consumption by replacing existing steel and aluminum materials. However, Mg species are susceptible to corrosion, especially in harsh environments (high-temperature or acidic), severely limiting the range of practical applications. Here, 2D covalent organic framework (COF) is synthesized with pore diameters ranging from 1.5 to 2.9 nm to obtain ultrafast nanofluidic channels. Loaded with silver (Ag+) ions, 2-mercaptobenzimidazole (2-MB) inhibitors are immobilized in the COF channels through the silver bridges. Based on the strong metal-complexing capability, Ag+ ions precipitated with various corrosive media (Cl-, Br-, I-, SO3 2-, S2-, S2O3 2- SO4 2-, CO3 2-, PO4 3-); meanwhile, the 2-MB inhibitors are rapidly released through the nanofluidic channels, forming a passivation film as a corrosion barrier to protect the Mg substrate. After integration with commercial polyethersulfone (PES), the COF-based coating exhibits high repairing capability achieving 100% damage restoration within 7 h, outperforming all existing coatings of Mg alloys. Notably, the coating shows almost complete protection of Mg alloys after being treated in respective 473 K, acidic (pH ≈4.0), and alkaline (pH ≈10.0) environments.

RESUMEN

Cryogenic detection technology is essential to ensure safety and effectiveness in fields such as medical refrigeration, cold chain transport, and cryogenic bioengineering. In this paper, a time-responsive visual cryogenic detection strategy is developed based on the storage properties of CaZnOS: Pb2+, Pr3+ phosphors with shallow traps. Since the carrier release rate from the trap center receives the influence of ambient temperature and storage time, the storage time of the temperature-sensitive product can be determined by the different optical signals of CaZnOS: Pb2+, Pr3+ phosphors obtained under 980 nm laser irradiation. In addition, CaZnOS: Pb2+, Pr3+ phosphors with multimode luminescence enable time-responsive visual detection of ambient temperature under extreme conditions. This work not only demonstrates the potential of CaZnOS: Pb2+, Pr3+ phosphors for visual detection of temperature and time but also paves the way for the development of various applications relying on cryogenic monitoring.

RESUMEN

This study presents the use of nanoscale covalent organic frameworks (nCOFs) conjugated with tumor-targeting peptides for the targeted therapy of triple-negative breast cancer (TNBC). While peptides have previously been used for targeted delivery, their conjugation with COFs represents an innovative approach in this field. In particular, we have developed alkyne-functionalized nCOFs chemically modified with cyclic RGD peptides (Alkyn-nCOF-cRGD). This configuration is designed to specifically target αvß3 integrins that are overexpressed in TNBC cells. These nCOFs exhibit excellent biocompatibility and are engineered to selectively disintegrate under acidic conditions, allowing for precise and localized drug release in tumor environment. Doxorubicin, a chemotherapeutic agent, has been encapsulated in these nCOFs with high loading efficiency. The therapeutic potential of Alkyn-nCOF-cRGD has been demonstrated in vitro and in vivo models. It shows significantly improved drug uptake and targeted cell death in TNBC, highlighting the efficacy of receptor-mediated endocytosis and pH-controlled drug release. This strategy leverages the unique properties of nCOFs with targeted drug delivery to achieve significant advances in personalized cancer therapy and set a new standard for precision chemotherapeutic delivery.